Clinical pharmacokinetics and pharmacodynamic target attainment of pazufloxacin in prostate tissue: Dosing considerations for prostatitis. Issue 12 (December 2017)

• Record Type: Journal Article
• Authors: Nakamura, Kogenta; Ikawa, Kazuro; Nishikawa, Genya; Kobayashi, Ikuo; Narushima, Masahiro; Muramatsu, Hiroyuki; Morinaga, Shingo; Kajikawa, Keishi; Kato, Yoshiharu; Watanabe, Masahito; Zennami, Kenji; Kanao, Kent; Morikawa, Norifumi; Sumitomo, Makoto
• Is Part Of: Journal of infection and chemotherapy. Volume 23:Issue 12(2017:Dec.)
• Page Start: 809
• Page End: 813
• Publication Date: 2017-12
• Subjects: Pazufloxacin -- Pharmacokinetics/pharmacodynamics -- Prostatitis -- Transurethral resection of the prostate; Chemotherapy -- Periodicals; Infection -- Periodicals; Communicable diseases -- Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1016/j.jiac.2017.08.005
• Languages: English
• ISSNs: 1341-321X

Abstract

Abstract: The present study examined the clinical pharmacokinetics of pazufloxacin in prostate tissue and estimated the probability of target attainment for tissue-specific pharmacodynamic goals related to treating prostatitis using various intravenous dosing regimens. Patients with prostatic hypertrophy received prophylactic infusions of pazufloxacin (500 mg, n = 23; 1000 mg, n = 25) for 0.5 h prior to transurethral prostate resection. Drug concentrations in plasma (0.5–5 h) and prostate tissue (0.5–1.5 h) were measured by high-performance liquid chromatography and used for subsequent noncompartmental and three-compartmental analysis. Monte Carlo simulation was performed to evaluate the probability of target attainment of a specific minimum inhibitory concentration (MIC) in prostate tissue: the proportion that achieved both area under the drug concentration over time curve (AUC)/MIC = 100 and maximum concentration (Cmax )/MIC = 8. Prostatic penetration of pazufloxacin was good with mean Cmax ratios (prostate tissue/plasma) of 0.82–0.99 and for AUC, 0.80–0.98. The probability of reaching target MIC concentrations in prostate tissue was more than 90% for dosing schedules of 0.25 mg/L for 500 mg every 24 h (500 mg daily), 0.5 mg/L for 500 mg every 12 h (1000 mg daily), 1 mg/L for 1000 mg every 24 h (1000 mg daily), and 2 mg/L for 1000 mg every 12 h (2000 mg daily). Importantly, the 2000 mg daily regimen of pazufloxacin produced a profile sufficient to have an antibacterial effect in prostate tissue against clinical isolates of Escherichia coli and Klebsiella pneumonia with MIC values less than 2 mg/L.